| Project/Area Number |
11470197
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES |
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Principal Investigator |
ANDO Koichi National Institute of Radiological Science, Researcher, 国際宇宙放射線医学研究センター, 研究員 (00159526)
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| Co-Investigator(Kenkyū-buntansha) |
MAJIMA Hideyuki National Institute of Radiological science, Researcher, 国際宇宙放射線医学研究センター, 研究員 (60165701)
AKASHI Makoto National Institute of Radiological Sciences, Researcher, 放射線障害医療研究部, 研究員 (10670979)
TANISHITA Kazuo Keio University, Department of System Design Engineering, Professor, 理工学部, 教授 (10101776)
明石 真言 放射線医学総合研究所, 放射線障害医療研究部, 研究員 (10222514)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | carbon ions / oxygen consumption / OER / PR-350 / LET / MnSOD / transription factor / H2O2 / 2-ニトロイミダール / 増殖死 / 活性酸素 / H2O2 / マウス繊維肉腫 / ガンマ線 / 解糖系酵素 / 血管形成 / TNF |
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| Research Abstract |
The murine NFSa fibrosarcomas under condition of clamped hypoxia developed less apoptosis at 2 days after irradiation than those under air-breathing condition. The clamped hypoxia did not, however, affect apoptosis developing 3 days or later, suggesting that several mechanisms are involved in tumor reoxygenation. The oxygen consumption of tumor cells was more effectively reduced by high let carbon ions than X rays, suggesting a possibility that the accelerated reoxygenation by carbon irradiation could be due to the reduced oxygen consumption. Apoptosis of cultured V79 Chinese hamster cells after irradiation showed that the oxygen enhancement ration(OER) for carbon ions and X rays was the same, i.e., 2.5. A hypoxic radiosensitizer PR-350 enhanced apoptosis of hypoxic V79 cells after X-ray irradiation, but not after carbon-ion irradiation. When colony formation was studied, OER of V79 cells was 3.0 and 2.0 after X- and carbon-irradiation, respectively. The sensitizing activity of PR-350 was 1.5 and 1.3 for X- and carbon-irradiation, respectively. Apoptosis seems to be less influenced than reproductive death by oxygen condition and LET. Human monocytic leukemia, cells THP-1 responded to X-ray Irradiation such that activation of a transcription factor NFkB was associated with reduction of IkB. As the activation of NFkB is reported to inhibit TNF-mediated apoptosis, X-ray irradiation could activate both apoptosis and anti-apoptosis signaling pathway. Human ovarian cancer cells, which was transfected and over-expressing manganese superoxide dismutase (MnSOD) genes, showed retarded growth and increased radiosensitivity, comparing with vector-transfected control cells. The increased radiosensitivity was due to apoptosis which was associated with the overproduction of H2O2.
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